The end is near

On Saturday the decision was made between all of the doctors, Mira (my daughter and Elizabeth's step-daughter) and me that Elizabeth's condition is irreversible and that we should focus exclusively on palliative care to make her last time more comfortable and without pain. She had by then lost all cognitive function and was totally unresponsive to any stimuli except pain. Indeed, she seemed at times in terrible agony -- it was horrible for all of us to watch. We disconnected all of the curative IV's and started with periodic injections of morphine and ativan. These would work for a while but quickly wore off and left her again in pain as evaluated by her contorted face and arm motions.

Yesterday afternoon we started a continuous IV drip of morphine, at first at 2 ml/hr gradually increased to 2.7 ml/hr currently. On other advice, we stopped the ativan. During the day today this has been very successful; she has slept peacefully the entire day. Her respiration rate has slowed to 4-5 breaths/hour, which everyone agrees is not due to this relatively small dose of morphine but to a general slowing of bodily function as her body shuts down. We have consulted with the palliative care department and they are alerted if the need for stronger analgesics arises.

No one knows for certain, of course, but expert estimates are that she will die within a few days and possibly within hours. It is a very sad time for us all, but it has been inspiring to see the many of her friends and colleagues that have come to visit and often to stay for long periods. Of course, we are no longer concerned with visitors bringing infection.

According to her wishes (and mine as well) she will be cremated and there will be no funeral. There will probably be a memorial later in the fall that will have both a personal and a professional component, but there are no definite plans as yet.

Continuing Downhill

Elizabeth's condition seems to be getting slowly worse each day. She is now completely immobile in bed and cognitively very impaired. It is not clear that she understands much of what goes on around her and is mainly unresponsive to questions or comments -- occasionally she will answer with a shake or nod of the head. She does object strenuously to the necessary caretaking routines which probably cause her pain and/or anxiety, but we aren't really sure.

No one really understands the causes of this state -- they could be the effect of the leukemia actually entering the brain, but they could also be due to the toxic mix of medications she has been getting, including steroids, chemo, antibiotics, ativan, IV nutrition, etc. Another possibility is that all of the above have put such a strain on her body that it is simply in the process of shutting down.

Although we will be continuing as now for a few days unless things get suddenly worse, it seems quite possible, even likely, that she will die in a relatively short time. We do not intend to apply extraordinary measures to keep her alive unless there is good reason to believe that she has a good chance for a full recovery given a bit more time, something that seems pretty distant as of today.

A difficult week

Just as her hospital stay was beginning, Elizabeth began to develop new symptoms of gastro-intestinal distress -- first reduced appetite, then nausea and vomiting and finally diarrhea. Although these were similar to the symptoms a couple of months ago that were determined to be GVHD, the docs are still unclear if this is the cause now or something else. Although the nausea/vomiting has pretty much disappeaed, the diarrhea remains and is making life entirely miserable for her. Se is being treated for several possible causes including GVHD (steroids again) and infection (antibiotics). Both the illness and the treatments make her very weak and tired, barely able to get out of bed. To ice the cake, she has now developed a severe hoarseness that makes it hard and eventually painful to talk much. She will get a colonoscopy Monday to take biopsies which will determine definitively whether or not it is GVHD. She is still unable to take more than a clear-liquid diet. In addition to all the meds, she has had several infusions of platelets and is due for some red blood cells; at one time there were 5 IV pumps running at one time.

This is all, of course, a sideshow to the main event of trying to treat the relapsed leukemia. The first part of this proceeded uneventfully -- as expected the anti-survivin drug (which almost universally the staff refer to as "survivin", a logical fallacy painful to my logician soul) had no observable side effects -- well probably not. The troubling point that developed over the period, although it is not thought to be due to the drug, was a big spike in her liver enzymes. There seem to be no good theories what caused this, but it was bad enough yesterday that the planned start of the chemotherapy sequence was put on hold. Fortunately (one of the few bits of good news this week) they were down substantially today and they have as I write started the chemotherapy. We have now to hope that the liver problems stay fixed at least long enough to complete the 3 days of chemo.

Admission

Elizabeth was admitted on Monday afternoon. Her room is 8431 (unit 8B) with phone 734-936-8431.

She is currently undergoing some tests preparatory to the procedure -- some are for her benefit, some for the research study. She is scheduled to get the experimental drug (imaginatively called LY2181308) tomorrow through Friday, then get chemo Friday-Sunday. According to a press release

LY2181308 targets survivin, a molecule that supports the survival of cells that would normally die through programmed cell death or apoptosis. Survivin helps in the abnormal growth of cancer cells, and is abundant in many types of cancers, including colon, brain, lung, skin and others, but nearly nonexistent in normal cells and tissues.

Phase 1 trials have shown that survivin is indeed reduced by the treatment, but these are the first trials that test whether this decrease will really lead to increased effectiveness of the following chemotherapy. Stay tuned.

Another way forward

After consultation with the hematologist Harry Erba that we saw at the beginning of this process, Elizabeth (with my full agreement) has decided to undertake another round of chemotherapy. This will involve two of the same agents she received in the first two rounds, idarubicin and cytarabine, but also a brand new experimental drug. The experimental drug is intended to reduce the ability of the leukemia cells to develop resistance to being killed by the chemo, a common problem in the treatment of recurring leukemia. There is essentially no data on this drug -- this is a phase 2 clinical trial -- but there seems to be little risk and it might do some good. The chemo portion is the standard chemo they would use for relapsed AML. Depending on the outcome of the chemo we will then decide where to go from there. It is still possible that she might get a second transplant preceded by a less rigorous and more survivable conditioning, but the more we read from the literature it seems that there is little evidence that second transplants are successful.

The chemo must be done as an inpatient, so she will probably be admitted to the hospital again early next week. The predicted stay is 3-4 weeks, but of course it all depends on how things go. Because of the presence of the transplanted donor cells, with the accompanying graft-versus-host disease, chemo at this stage is considerably different from the earlier ones and perhaps less predictable. She is already showing quite noticeable effects of graft vs host disease, which means the donor cells should attack the leukemic cells along with the chemotherapy.

Note that I have changed the photo link at the top right -- in place of just a couple of albums, I now have a link to a new gallery with many of my photos from the past several years. If you have some browsing time, have a look.

A Major Setback

We found out on Friday that Elizabeth's leukemia has returned. This was surprising since both the 30 and 100 day tests showed that her marrow cells were 100% donor with none of her old leukemic cells showing up. But somehow there were some of hers left and they have done what they do and multiplied quickly to the point that they now dominate the marrow. This is regarded as very bad with a poor prognosis. We talked with two doctors today and hope to meet with a third in the next couple of days. As we understand it now there are basically two options.

1. Apply palliative care to contain the leukemic cells for a short time (a few months at most) to enable a more comfortable end of life. This might or might not enable us to spend some time away in some interesting and fun place to enjoy our last time together -- it would depend on what the palliative care involved, information we are currently lacking.

2. Give aggressive chemotherapy, stronger than any she has had to date, followed by a second marrow transplant. The original donor cells were roughly double the amount they wanted to infuse for the first transplant, so an equivalent amount was frozen to hold for such an occasion. There is considerable opinion that the chemotherapy itself might be too much for her body to endure -- organ failures are common, especially among people her age and those who have already suffered some organ injury as she has with the liver reactions to massive antibiotics to fight an earlier infection. If she survived the chemo and transplant, it would still be expected that she would have multiple problems over many months, perhaps a year, some of which could kill her then.

Obviously neither option is remotely appealing, but it seems to be where we are now. It is very disappointing, since we were beginning to allow ourselves to think that we were past the worst of the process, but it seems that is still to come. We are still looking for a few more pieces of information, such as the actual data on survival rates for option 2. The doctor reasonably wants us to make a decision over the next week.